PROJECT SUMMARY/ABSTRACT Cigarette smoking among U.S. adolescents has declined, but similar declines have not occurred in youth smokeless tobacco (ST) use. There is also a growing trend among adolescents and young adults of poly-use of multiple tobacco products in combination. In recent decades, ST use has shifted from an older to a younger demographic, coincident with increasing industry marketing and expanding diversity in ST product characteristics. These new ST products include different types, brands, flavors, and varying levels of bioavailable nicotine and cancer-causing nitrosamines. There is a need for independent data on how these differentiating characteristics of ST and emerging tobacco products contribute to youth perceptions, initiation, established use, poly-use, and ultimately, exposure to nicotine and carcinogens over time. This project will address this research gap via three specific aims: (1) Identify the impact of ST and other tobacco product characteristics, including packaging, characterizing flavors, and product design, on rural adolescents' perceived harm, acceptability, and appeal of current and emerging smokeless, combustible, and alternative tobacco products to; (2) Prospectively characterize tobacco use behaviors over time (e.g., initiation, cessation, changes in intensity, product switching, and poly-use) and how family and social factors and specific product characteristics predict transitions in behavior; and (3) Evaluate the impact of use of specific tobacco products and product types on rural adolescents' exposure to nicotine and tobacco-specific nitrosamines, including use of potential new products. This study will include a school-based prospective cohort of 1500 adolescents attending rural high schools, followed for 5 survey waves over 24 months. Qualitative studies with adolescents and their parents/guardians will be nested in the cohort to provide greater depth of understanding of how product characteristics and socio-contextual factors influence perceptions and behavioral decisions regarding tobacco products. Collected biomarkers will reveal how exposure to nicotine and nitrosamines varies with differences in use patterns and difference in products. This project will improve understanding of how different characteristics of ST and emerging tobacco products impact behavior and health effects by measuring perceptions, behaviors, and exposure to nicotine and nitrosamines. This project will generate evidence relevant to potential regulation of and public communication on current and emerging tobacco products and will contribute behavioral and health outcome data for use in economic models of impact. Such evidence will inform FDA regulation of the characteristics of ST and other tobacco products so as to reduce youth initiation and inform FDA communication strategies for rural populations.